| Status | 已發表Published |
| Title | Interaction of combined glycyrrhizic acid on the pharmacokinetics and the hepatotoxicity of methotrexate |
| Author | Xiong, S.H. ; Yu, H.
|
| Date Issued | 2021-08-01 |
| Keyword | Methotrexate Glycyrrhizic acid Drug-drug interaction Pharmacokinetics Hepatotoxicity |
| Abstract | Methotrexate (MTX) is an FDA-approved folic acid antagonist and is a recommend anchor disease-modifying anti-rheumatic drug (DMARD) for clinical management of rheumatoid arthritis (RA). MTX-associated hepatotoxicity is the most observed adverse effects during the MTX therapy, and pre-treatment with glycyrrhizic acid (glycyrrhizin, GA) is believed to attenuate the MTX-induced hepatotoxicity. Chapter 1 briefly introduces the background of methotrexate and glycyrrhizic acid and expounds that choosing methotrexate combined with glycyrrhizic acid in the treatment of rheumatoid arthritis is a feasible method in clinic. And then it's included the research objective and goals, research methodology and design, organization of this thesis. Chapter 2 describe the establishment of an UPLC-MS/MS analytical method for the determination of drug content in biological samples. These include optimization of liquid-phase methods and mass spectrometry conditions, configuration of standard solution, preparation and handling of samples, and methodological validation. And the biopharmaceutical interaction between methotrexate and glycyrrhizic acid. Including the influence of GA on the pharmacokinetics of MTX were investigated both in vitro and in vivo. The results indicated that GA could increase the intestinal absorption of MTX by modulating the multidrug resistance ‐ associated proteins (MRPs)-mediated drug efflux and the plasma protein binding of MTX, but did not effect on the oral bioavailability and in vivo elimination of MTX from plasma in rats. Chapter 3 describe the effect of glycyrrhizic acid on the liver protection of methotrexate. Pretreated glycyrrhizin can effectively reduce the cytotoxicity of methotrexate in human normal liver cells LO-2. Moreover, GA effectively reduced the MTX-induced hepatotoxicity by improving liver function indicators (aspartate aminotransferase/AST and alkaline phosphatase/AKP) and histological injure of liver. Chapter 4 A summary of the paper, including the contributions of this paper, the shortcomings of current research, and expectations for future work. In summary, this study provides a knowledge on better understanding the influence of GA on the iv pharmacokinetics and hepatotoxicity of MTX in vivo, which is very helpful for the further clinical application of the combined GA and MTX for RA therapy. |
| Language | 英語English |
| PUB ID | 59974 |
| Document Type | Thesis |
| Collection | Institute of Chinese Medical Sciences |
| Recommended Citation GB/T 7714 | Xiong, S.H.,Yu, H.. Interaction of combined glycyrrhizic acid on the pharmacokinetics and the hepatotoxicity of methotrexate[D], 2021. |
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